The overall goal of the Biocompatibility Group will be to evaluate the biocompatibility of dental materials which are developed to be used in restorative dentistry, either as restorative materials or as materials to treat the walls of cavities before placement of restorations. Inconsistencies in the responses of odontoblasts to outside insults (e.g. exposure of dentinal tubules and thus odontoblasts to outside environment following caries or a restorative procedure) is observed in variation in the thickness of reparative dentin. In fact, from clinical anecdotal evidence, no generalizations can be made about the reparative dentin response to presence of bacterial or synthetic materials in the cavity preparation. During this second five-year period, we are proposing to study long term effects of materials on odontoblast differentiation, in addition to the more acute or short-term studies which are used routinely for materials testing in our laboratory at the present time. Thus, primary cultures of fetal mouse odontoblasts, as well as established clones of these cells, will be grown and characterized by various mRNA probes and metabolic probes during the proliferative stage, the stage of production of the extracellular matrix, and finally the mineralization stage of these cells in culture. Then, these same probes will be used to measure the effects of various components of resins, bonding agents, silanating agents, and other restorative materials upon the sequences of differentiation and metabolism of these odontoblasts cultures. It is the intent of this project to identify the effects of these materials on differentiation and function, and gene expression of odontoblasts which will suggest mechanisms by which materials have long term, sublethal effects on the ability of these cells to respond to injury. The development of such a perspective may give us additional methods (alternates to cytotoxicity testing) of evaluating materials and more accurate tests with which to predict the efficacy of long term treatment of teeth as well as better, safer materials.